Submission Number: TRI-4-16-7

Abstract Number: 507

ROLE OF ESTROGEN RECEPTOR ALPHA (ER) IN WHITE ADIPOSE TISSUE (WAT) DEPOSITION IN MICE.

PA Heine ¹, Dennis B Lubahn* ², DH Keisler* ³, M Hufford ² and Paul S Cooke* ¹

Dept. of Veterinary Biosciences, Univ. of Illinois, Urbana, IL ¹
Depts. of Biochemistry & Child Health, Univ. of Missouri, Columbia, MO ²
Dept. of Animal Science, Univ. of Missouri, Columbia, MO ³

Abstract:
We have previously reported preliminary data indicating that 6-month-old male ER knockout (ERKO) mice have twice as much white adipose tissue (WAT) as wild-type (WT) mice. In the present study, we examined 1) the time course of the WAT increase in males; 2) whether there is also an increase in brown adipose tissue (BAT); 3) whether female ERKO mice also show increases in WAT and 4) whether the increases in WAT are accompanied by changes in food consumption and/or circulating leptin levels. Neonatal male ERKO mice do not show an increase in WAT compared to WT mice, but the WAT increase is measurable at 30 days and increases with age. BAT is not increased in male or female ERKO mice. Similar to ERKO males, 90-day-old female ERKO mice have a 100% increase in WAT compared to age-matched WT females, although the increase is greater in the subcutaneous WAT than seen in the males. To elucidate the mechanism of this effect, we conducted a longitudinal feeding study and compared circulating leptin levels in male ERKO and WT mice. The feeding study (n=5 sibling pairs) indicated that ERKO mice weigh less than WT mice from birth until 1-2 months of age. The ERKO mice gain weight more quickly than WT mice and after 2 months of age, ERKO males weigh more than WT siblings. This discrepancy in weight increases with age. Food consumption does not change during the post-weaning period in ERKO males over time, but decreases slightly in WT mice over time. Leptin values, taken from both sexes at several ages, indicate no correlation between genotype and circulating leptin values. Thus, the expected increase in leptin levels is not seen in ERKO mice despite increased WAT, and these animals remain hyperphagic compared to WT controls despite increased WAT stores. These data suggest that normal homeostatic mechanisms for food consumption and WAT deposition are altered in ERKO males, though the mechanism by which lack of ER results in these changes remains unclear. .

Keywords: leptin, fat, male, appetite, brown adipose tissue

This abstract is being presented at: 8:00 AM in session:
Hormone Receptors